Drugs Affecting Gastrointestinal Secretions PDF

Chapter 57 Drugs Affecting Gastrointestinal Secretions Copyright Copyright © 2017 © 2012 Wolters Wolters Kluwer Kluwer All Health Rights...

Chapter 57 Drugs Affecting Gastrointestinal Secretions Copyright Copyright © 2017 © 2012 Wolters Wolters Kluwer Kluwer All Health Rights Reserved | Lippincott Williams & Wilkins Underlying Causes of GI Disorders Dietary excess Stress Hiatal hernia Gastroesophageal reflux Peptic ulcer disease Adverse drug effects Copyright © 2023 Wolters Kluwer All Rights Reserved GERD and Ulcer Disease  Drugs used to affect GI secretions o Decrease GI secretory activity o Block the action of GI secretions o Form protective coverings on the GI lining to prevent erosion from GI secretions  Drug classes o Histamine-2 agonists o Antacids o Proton pump inhibitors o Gastrointestinal protectants o Prostaglandins Copyright © 2023 Wolters Kluwer All Rights Reserved Use of Agents Affecting Gastrointestinal Secretions Across the Lifespan Copyright © 2023 Wolters Kluwer All Rights Reserved Sites of Actions of Drugs Affecting Gastrointestinal Secretions Copyright © 2023 Wolters Kluwer All Rights Reserved Histamine-2 (H2) Antagonists #1 Block the release of hydrochloric acid in response to gastrin Drugs o Cimetidine (Tagamet HB) o Famotidine (Pepcid AC) o Nizatidine (Axid AR) o Oral formulations available as OTC medications o Ranitidine (Zantac) was withdrawn from market Copyright © 2023 Wolters Kluwer All Rights Reserved Histamine-2 (H2) Antagonists #2 Therapeutic actions o Selectively block H2 receptors  Prevents about 70% of hydrochloric acid release  Decreases pepsin production Copyright © 2023 Wolters Kluwer All Rights Reserved Histamine-2 (H2) Antagonists #3  Indications o Short-term treatment of active duodenal ulcer or benign gastric ulcer o Treatment of pathological hypersecretory conditions such as Zollinger–Ellison syndrome o Prophylaxis of ulcers induced by stress or NSAID use and acute upper GI bleeding in critical patients o Treatment of erosive GERD o Treatment of ulcers caused by H. pylori o Relief of symptoms of heartburn and indigestion Copyright © 2023 Wolters Kluwer All Rights Reserved Histamine-2 (H2) Antagonists #4 Pharmacokinetics o Vary by specific drug o Cross placenta and enter human milk Contraindications o Known allergy Cautions o Pregnancy or lactation o Hepatic or renal dysfunction o Prolonged or continual use Copyright © 2023 Wolters Kluwer All Rights Reserved Histamine-2 (H2) Antagonists #5 Adverse effects o GI effects o CNS effects o Cardiac arrhythmias and hypotension o Gynecomastia and impotence Drug–drug interactions o Cimetidine slows metabolism of various drugs o Nizatidine and aspirin Copyright © 2023 Wolters Kluwer All Rights Reserved Histamine-2 (H2) Antagonist Prototype Copyright © 2023 Wolters Kluwer All Rights Reserved Question #1 Which H2 inhibitor is available in both oral and parenteral forms? A. Famotidine B. Cimetidine C. Nizatidine D. Lansoprazole Copyright © 2023 Wolters Kluwer All Rights Reserved Answer to Question #1 A. Famotidine Rationale: Famotidine is available in oral and parenteral forms. Nizatidine and cimetidine are available only in oral form. Lansoprazole is available in both forms but is a proton pump inhibitor. Copyright © 2023 Wolters Kluwer All Rights Reserved Antacids #1 A group of inorganic chemicals that neutralize stomach acid Available OTC; many people use them to self-treat variety of symptoms Drugs o Sodium bicarbonate (generic) o Calcium carbonate (Oystercal, Tums, and others) o Magnesium salts (Milk of Magnesia and others) o Aluminum salts (Amphojel and others) Copyright © 2023 Wolters Kluwer All Rights Reserved Antacids #2 Therapeutic actions o Neutralize stomach acid by direct chemical reaction Indications o Symptomatic relief of upset stomach associated with hyperacidity o Relief of symptoms associated with hyperactivity (as in peptic ulcer, gastritis, etc.) Pharmacokinetics o Vary by specific drug Copyright © 2023 Wolters Kluwer All Rights Reserved Antacids #3 Contraindications o Allergy Cautions o Any condition that can be exacerbated by electrolyte or acid–base imbalance o Electrolyte imbalance o GI obstruction o Renal dysfunction o Pregnancy and lactation Copyright © 2023 Wolters Kluwer All Rights Reserved Antacids #4  Adverse effects o Relate to their effects on acid–base and electrolyte balance o Rebound acidity with frequent use o Alkalosis o Hypercalcemia o Constipation or diarrhea o Hypophosphatemia  Drug–drug interactions o Affect the absorption of many other drugs Copyright © 2023 Wolters Kluwer All Rights Reserved Antacid Prototype Copyright © 2023 Wolters Kluwer All Rights Reserved Proton Pump Inhibitors #1 Suppress secretion of hydrochloric acid into the lumen of the stomach Drugs o Omeprazole (Prilosec) o Esomeprazole (Nexium) o Lansoprazole (Prevacid) o Dexlansoprazole (Dexilant) o Pantoprazole (Protonix) o Rabeprazole (Aciphex) Copyright © 2023 Wolters Kluwer All Rights Reserved Proton Pump Inhibitors #2  Therapeutic actions o Specifically inhibit the H+, K+–ATPase enzyme system on the secretory surface of gastric parietal cells  Blocks final step of acid production  Indications o Short-term treatment of active duodenal ulcers, GERD, erosive esophagitis, and benign active gastric disease o Long-term treatment of pathological hypersecretory conditions o Maintenance therapy for erosive esophagitis and ulcers  Pharmacokinetics o Acid labile, rapidly absorbed from GI tract o Metabolized in the liver and excreted in the urine Copyright © 2023 Wolters Kluwer All Rights Reserved Proton Pump Inhibitors #3  Contraindications o Allergy o Concurrent use with medications containing rilpivirine  Cautions o Pregnancy or lactation  Adverse effects o Related to effects on H+, K+–ATPase pump on the parietal and other cells o CNS effects o GI effects o Upper respiratory tract symptoms o Other less common effects o Long-term use: increase in bone loss, hypertension Copyright © 2023 Wolters Kluwer All Rights Reserved Proton Pump Inhibitors #4 Drug–drug interactions o Benzodiazepines, phenytoin, warfarin o Ketoconazole, theophylline o Some antiretroviral medications Copyright © 2023 Wolters Kluwer All Rights Reserved Proton Pump Inhibitor Prototype Copyright © 2023 Wolters Kluwer All Rights Reserved GI Protectant #1 Coat any injured area in the stomach to prevent further injury from acid Only one available: sucralfate (Carafate) Copyright © 2023 Wolters Kluwer All Rights Reserved GI Protectant #2  Therapeutic actions o Forms an ulcer-adherent complex at duodenal ulcer sites, protecting the sites against acid, pepsin, and bile salts  Prevents further breakdown and promotes healing o Inhibits pepsin activity in gastric juices  Indications o Treatment of ulcers  Pharmacokinetics o Minimally absorbed o Most excreted via feces; small amount absorbed is excreted in urine Copyright © 2023 Wolters Kluwer All Rights Reserved GI Protectant #3 Contraindications o Allergy o Renal failure Cautions o Pregnancy or lactation Copyright © 2023 Wolters Kluwer All Rights Reserved GI Protectant #4 Adverse effects o GI effects (constipation most frequently seen) o Other effects: dizziness, sleepiness, vertigo, skin rash, back pain Drug–drug interactions o Aluminum salts o Phenytoin, digoxin, warfarin, fluoroquinolone antibiotics, or penicillamine Copyright © 2023 Wolters Kluwer All Rights Reserved GI Protectant Prototype Copyright © 2023 Wolters Kluwer All Rights Reserved Question #2 Please answer the following statement as true or false. There is a drug–drug interaction between warfarin and sucralfate. Copyright © 2023 Wolters Kluwer All Rights Reserved Answer to Question #2 True Rationale: If phenytoin, digoxin, warfarin, fluoroquinolone antibiotics (e.g., ciprofloxacin, norfloxacin), or penicillamine is combined with sucralfate, decreased serum levels and drug effectiveness may result. In such combinations, the individual agents should be administered separately with at least 2 hours between drugs. Copyright © 2023 Wolters Kluwer All Rights Reserved Prostaglandin #1 Protect the stomach lining One available for this use: the synthetic prostaglandin E1 analogue misoprostol (Cytotec) Copyright © 2023 Wolters Kluwer All Rights Reserved Prostaglandin #2  Therapeutic actions o Inhibits gastric acid secretion o Increases bicarbonate and mucous production in the stomach  Indications o Prevention of NSAID-induced gastric ulcers in patients at high risk for complications  Pharmacokinetics o Rapidly absorbed from GI tract o Metabolized in the liver; excreted in the urine o Crosses placenta; enters human milk Copyright © 2023 Wolters Kluwer All Rights Reserved Prostaglandin #3 Contraindications o Allergy o Pregnancy Cautions o Lactation o Hepatic or renal impairment Adverse Effects o Primarily related to GI effects o GU effects Copyright © 2023 Wolters Kluwer All Rights Reserved Prostaglandin Prototype Copyright © 2023 Wolters Kluwer All Rights Reserved Digestive Enzymes #1 Substances produced in the GI tract to break down foods into usable nutrients Two available o Saliva substitute (Aquoral, Moi-Stir, Mouth Kote, Salivart, others) o Pancrelipase (Creon, Pancreaze, Pertzye, Viokace, Zenpep) Copyright © 2023 Wolters Kluwer All Rights Reserved Digestive Enzymes #2 Therapeutic actions o Saliva substitute contains electrolytes and carboxymethylcellulose to act as a thickening agent in dry mouth conditions  Makes food bolus easier to swallow o Pancreatic enzymes are replacement enzymes that help the digestion and absorption of fats, proteins, and carbohydrates Indications o Replacement therapy Copyright © 2023 Wolters Kluwer All Rights Reserved Digestive Enzymes #3 Pharmacokinetics o Saliva substitute: not generally absorbed systematically; works when applied to mouth o Pancrelipase: thought to be processed through normal metabolic systems Contraindications o Allergy Cautions o Saliva substitute: HF, hypertension, or renal failure Copyright © 2023 Wolters Kluwer All Rights Reserved Digestive Enzymes #4 Adverse effects o Saliva substitute: complications from abnormal electrolyte absorption o Pancreatic enzyme: GI irritation (nausea, abdominal cramps, diarrhea) Copyright © 2023 Wolters Kluwer All Rights Reserved Digestive Enzyme Prototype Copyright © 2023 Wolters Kluwer All Rights Reserved Question #3 What H2 antagonist has been associated with antiandrogenic effects? A. Famotidine B. Cimetidine C. Nizatidine D. Ranitidine Copyright © 2023 Wolters Kluwer All Rights Reserved Answer to Question #3 B. Cimetidine Rationale: Cimetidine has been associated with antiandrogenic effects, including gynecomastia and galactorrhea. Copyright © 2023 Wolters Kluwer All Rights Reserved